ABSTRACT Childhood obesity is a significant public health problem that predisposes to adult obesity and serious obesity-related diseases. Obesity is particularly common in low-income families and children of obese parents, who also report higher levels of stress. High stress in parents is associated with decreased physical activity, overeating, and increased weight in parents and their children. While nutrition and behavioral preventions have been tested for low-income families, parent stress has not been targeted in highly stressed, low-income obese parents of at-risk preschoolers. In a previous pilot R21 project, we developed a novel program, Parenting Mindfully for Health, that targets parent stress and includes Nutrition and physical activity counseling (PMH+N), to reduce stress, improve parenting and healthy family choices to prevent childhood obesity in 2-5-year-old children. Findings indicated that PMH+N is feasible, acceptable, and improved parent stress and parenting to prevent increases in child body mass index (BMI) percentile relative to the contact Control with Nutrition (C+N). Building on promising preliminary findings, we now propose a 5-year R01 project to assess PMH+N vs. C+N in a large sample of parent-child dyads, and including a long-term 2-year follow-up to establish enduring effects of PMH+N on reducing parent stress, improving parenting to promote healthy eating and physical activity (PA) in parents and children, and in turn, prevent childhood obesity risk in preschoolers from highly-stressed, low- income families. Low-income, highly-stressed, obese parent-child dyads (N=240, children aged 2-5) will be randomly assigned to receive a 12-week PMH+N or C+N intervention and participation in a Toy Wait Task(TWT) challenge to assess observed parent-child interaction as a bio-behavioral measure pre/post intervention to assess parenting and stress responses. The following specific aims will be addressed: (1) test the efficacy of 12-week PMH+N vs. C+N in reducing parent stress and improving parenting and health behaviors in parent and child to decrease childhood obesity risk; (2) examine parent stress response, observed parenting, and family food intake and physical activity as mediators of PMH+N vs. C+N effects on parent and child BMI; (3) examine the enduring effects of PMH+N vs. C+N on parenting and health behaviors and child BMI percentile in reducing obesity risk over a 2-year follow-up period; and (4) examine the enduring effects of changes on parent stress, parenting and health behaviors, parent weight and metabolic functioning post intervention during 2-year follow-up. Successful completion of the proposed interdisciplinary project will provide support for an innovative approach to decrease early childhood obesity risk in low-income, stressed families while also addressing stress and obesity in high-risk adult parents. Findings will provide critical longitudinal data on parent stress and family and parenting factors in the development of obesity in at-risk children, that may inform future public health interventions to curb the growing epidemic of obesity in children and adults.